FAK (pp125FAK) is a major signaling protein involved in cell- matrix adhesion. The proposed studies examine the role of FAK in cellular responses to vascular injury. The first specific aim is to define the mechanisms of FAK regulation of endothelial cell motility. Confocal and video microscopy and FAK-green fluorescent protein constructs will be used to track FAK dynamics and endothelial cell migration. The effects of FAK overexpression, and dominant negative FAK will be defined in motility assays. The second specific aim is to elucidate pathways of FAK signaling to the nucleus in the regulation of endothelial cell proliferation. FAK signaling will be manipulated by expression of exogenous FAK variants and of potential downstream signaling proteins. Cells will be evaluated for changes in bromodeoxyuridine incorporation and cyclin D1 expression. The in vitro modeling in the proposed project will allow us to define the consequences of the molecular manipulation of FAK signaling for each of the above components of cellular response to inflammatory vascular injury.